Experimental Primary Brain Calcification Model and Its Application to Pathogenesis Mechanism Analysis and Therapeutic Research

Primary Brain Calcification (PBC) is a neurodegenerative disorder of unknown etiology that results in bilateral calcifications within the brain. PBC symptoms vary, including Parkinsonian symptoms and psychiatric symptoms. Abnormalities in phosphate metabolism within the brain are hypothesized to be a mechanism underlying the onset of PBC, but the precise pathophysiological mechanism remains unclear. Furthermore, no fundamental treatment or therapeutic agent for PBC has been established. Previous studies have reported <i>SLC20A2</i>, <i>PDGFB</i>, <i>PDGFRB</i>, <i>XPR1</i>, <i>MYORG</i>, <i>JAM2</i>, <i>CMPK2</i>, and <i>NAA60</i> as causative genes for familial PBC. Elucidating the pathophysiological mechanisms of PBC and developing treatments and therapeutic agents requires appropriate experimental disease models. Knockout mice and mutant mice targeting familial causative genes have been reported to be useful as in vivo models of PBC. Furthermore, several disease-specific iPS cells for PBC have been reported, suggesting their potential utility as PBC models. This paper reviews each familial causative gene and current PBC models, including genetically modified animals and disease-specific iPS cells, and examines their usefulness for understanding disease mechanisms and advancing therapeutic research.